Palladium-catalyzed C-H activation/C-C cross-coupling reactions: Via electrochemistry

Article abstract of DOI:10.1039/c7cc07429h

Palladium-catalyzed C-H activation/C-C cross-coupling reactions typically require stoichiometric chemical oxidants and exogenous ligands. However, there are significant disadvantages associated with the use of traditional stoichiometric oxidants. To overcome these issues, we have developed an electrochemical strategy to achieve methylation and acylation.

Full text of DOI:10.1039/c7cc07429h

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Marilyn M. Olmstead, Alan L. Balch, Josep M. Poblet, Luis Echegoyenet al.
Reactivity differences of Sc3N@C2n (2n 68 and 80). Synthesis of the
first methanofullerene derivatives of Sc N@D5h-C80
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Palladium-Catalyzed C−H Activation/C–C Cross-Coupling Reactions
via Electrochemistry
Cong Ma,‡a Chuan-Qi Zhao,‡a Yi-Qian Li,bc Li-Pu Zhang,bc Xue-Tao Xu,bc Kun Zhang,bc and Tian-
Sheng Mei*a
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
a) Pioneering work on Pd-catalyzed C(sp2)–H cross-couplings (ref. 4)
Palladium-catalyzed C–H activation/C–C cross-coupling reactions
typically require stoichiometric chemical oxidants and exogenous
ligands. However, there are significant disadvantages associated
with the use of traditional stoichiometric oxidants. To overcome
these issues, we have developed an electrochemical strategy to
achieve methylation and acylation.
Me
B
H
Me
Pd(OAc)2 (10 mol%)
+
O
B
O
N
N
Cu(OAc)2 (1 equiv )
B
Me
Me
O
Benzoquinone (1 equiv)
72% yield
b) This study: C(sp2)–H couplings via anodic oxidation
OMe
OMe
Me
N
N
Me BF3K
Palladium-catalyzed C–H cross-coupling reactions have
developed into powerful transformations for the construction
of C–C bonds.1,2 Among the C
−C bond-forming C–H cross-
OMe
R
H
N
cat. Pd
Ph
O
anodic oxidation
R
couplings, C–H methylation of arenes could streamline access
to important biologically active small molecules.3 Toward that
end, in 2006, Yu and co-workers reported the first example of
Pd(II)-catalyzed aryl C(sp2)–H coupling with alkyl tin and alkyl
boron reagents (Scheme 1a).4 Following this seminal report by
Yu and co-workers, a number of examples of Pd-catalyzed aryl
C(sp2)–H couplings have been reported.5,6 However in order to
accomplish these transformations, in all cases a stoichiometric
amount of exogenous chemical oxidants including Cu and Ag
salts is need to oxidize Pd(0) to Pd(II). In some cases, a
benzoquinone (BQ) coadditive was shown to be crucial not
only for reoxidation of Pd(0) to Pd(II),4 but also for accelerating
reductive elimination.7 The addition of these oxidants results
in undesired byproducts, which is inherently atom
uneconomical. Moreover, the oxidant could obstruct the
catalytic system by coordinating the substrate.
O
R
Ph
CO2H
c) Mechanistic analysis
Me BF3K
ArPdIII Me
or
ArPdIV Me
ArPdII
anodic oxidation
A
(Path B)
C
Me BF3K
Ar Me
(Path A)
Ar Me
Pd0
PdI
PdII
ArPdII Me
or
anodic oxidation
B
Scheme 1. Pd-catalyzed C(sp2)–H cross-coupling reactions
transition-metal-catalyzed C–H functionalization is an
attractive approach.10,11 We recently demonstrated Pd-
catalyzed oxygenation via electrochemical oxidation.12 We
questioned whether this anodic oxidation system would be
compatible with aromatic C(sp2)–H cross-coupling reactions.
We report herein the first Pd-catalyzed C(sp2)–H couplings of
The recent years have witnessed
a
renaissance of
promising
electrochemical synthesis, representing
a
alternative to traditional chemical oxidants because it obviates
the use of wasteful and potentially toxic and dangerous
reagents.8,9 The utilization of electric current as an oxidant for
ketoximes with organoboron reagents or
α-keto acids via
anodic oxidation, in which electric current is used in place of
stoichiometric oxidants (Scheme 1b). Mechanistically, we
hypothesized that, following aromatic C(sp2)–H cleavage to
a.State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P.
R. China. E-mail: mei7900@sioc.ac.cn
give aryl palladium species
A
, transmetallation with potassium
Then
b.School of Chemical & Environmental Engineering, Wuyi University, Jiangmen,
529020, China
trifluoromethylborate could give Pd(II) complex
B.
reductive elimination could deliver the product and Pd(0),
which could then be oxidized by the anode to regenerate
c. International Healthcare Innovation Institute (Jiangmen), Jiangmen, 529000,
China
†Electronic Supplementary Information (ESI) available: CCDC 1550234. See
DOI: 10.1039/x0xx00000x
active Pd(II) species (Path
A, Scheme 1c). Alternatively,
intermediate
A
could undergo a transmetallation with MeBF3K
‡
These authors contributed equally.
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under anodic oxidation to produce
a Pd(III) or Pd(IV) obtained when MeB(OH)2 or (MeBO)3 was used instead of
intermediate C 13
after which reductive elimination could MeBF3K (entries 8, 9). No product was isolated when AcOH
,
deliver the product and regenerate the Pd (II) or Pd(I) catalyst. was replaced by other solvents such as DMF or
The Pd(I) species could be further converted into Pd(II) via trifluoroethanol (TFE) (entries 10, 11). Notably, the reaction
anodic oxidation (Path
B
, Scheme 1c).
could not proceed in the absence of electric current or
C(sp3) bonds, we Pd(OAc)2 (entries 12 , 13). Also no product was observed when
To investigate the formation of C(sp2)
−
chose oxime ether 1a as the substrate for the reaction with MnF3 was used as oxidant instead of electric current (entries
14, 15).6c
Table 1. Reaction optimization with substrate 1a
Various substituted oxime ethers were treated with MeBF3K
under the optimal reaction conditions and the corresponding
methylated derivatives 2b
Extending the alkyl chain bound to the O atom afforded 66–
75% yield of methylated products 2b ). Varying the
substituents at the -oxime ethers afforded 62–70% yield of
products (2e ). The addition of carbon-based substituents on
the phenyl group resulted in slightly lower yields (2j ). To our
–p were obtained (Table 2).
(
–d
α
–
i
–
n
delight, chloro and bromo substituents were tolerated in the
reaction system, although low yields were obtained due to
diminished reactivity (2o, 2p). Finally, when n-BuBF3K was used
instead of MeBF3K, the corresponding product was also
obtained in 44% yield (2q).
Table 2. Substrate scope of oxime ethers for aromatic C–H
alkylationa
aReaction conditions: 1 (0.3 mmol), Pd(OAc)2 (10 mol%),
MeBF3K (1.5 equiv), acetic acid (3 mL), K2HPO4 (3 equiv) and
KH2PO4 (3 equiv) [anode], K2HPO4 (1 equiv) and KH2PO4 (1
equiv), acetic acid (1 mL) [cathode] in an H-type divide cell
with two platinum electrodes and a Nafion 117 membrane, 60
°C. bThe yield was determined by GC with dodecane as the
internal standard. cIsolated yield in the parentheses.
MeBF3K under electrochemical conditions. As shown in Table
1, treatment of 1a (0.3 mmol) with MeBF3K (2 equiv) in the
presence of Pd(OAc)2 (10 mol%) under constant-current
electrolysis conditions at 1.5 mA (J = 0.75 mA·cm-2) gave 76%
(89% GC yield) monomethylated product 2a (entry 1). The GC
yield decreased to 75% when the amount of palladium catalyst
was decreased to 5 mol% (entry 2). Only trace product was
formed when Pd(OTf)2 was used instead of Pd(OAc)2 (entry 3).
Interestingly, the use of KH2PO4 or K2HPO4 individually
decreased the GC yield to 45% and 77% respectively (entries 4,
5). Increasing the electric current to 2.0 mA afforded 69% yield
(entries 6), and decreasing the electric current to 1.0 mA also
gave lower yield (54%, entry 7). No methylated product was
aReaction conditions:
1 (0.3 mmol), Pd(OAc)2 (10 mol%),
MeBF3K (2 equiv), acetic acid (3 mL), K2HPO4 (3 equiv) and
KH2PO4 (3 equiv) [anode], K2HPO4 (1 equiv) and KH2PO4 (1
equiv), acetic acid (1 mL) [cathode] in an H-type divide cell
with two platinum electrodes and a Nafion 117 membrane, 60
°C. Isolated yield.
Pd-catalyzed decarboxylative acylation of C(sp2)–H bonds
with α-oxocarboxylic acids has emerged as an attractive
synthetic method since it obviates the use of stoichiometric
2 | J. Name., 2012, 00, 1-3
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organometallic coupling reagents giving rise to CO2 instead of
A kinetic isotope effect (KIE) experiment was carried out
often toxic metal byproduct.14 These reactions also require (Scheme 4). The KIE was found to be kH/kD = 1.2, which
stoichiometric oxidants. Based on the proposed reaction indicates that the cleavage of the C–H bond may not be
pathway (Scheme 1c), we reasoned that it should be possible involved in the rate-determining step of the catalytic cycle.17
to achieve decarboxylative couplings to C–H bonds under
anodic oxidation conditions. To test this idea, we evaluated
decarboxylative couplings of oxime ethers
(
1
)
with
phenylglyoxylic acid (3) and were pleased to find that acylation
took place smoothly under anodic oxidation (See the
Supporting Information for optimization of these reaction
conditions). A variety of functional groups, including alkyl,
ester, chloro, bromo, fluoro and trifluoromethyl, were well
tolerated in the reaction system (Table 3).
Table 3. Substrate scope of oxime ethers for benzoylationa
Scheme 2. Stoichiometric formation of C(sp2)–Pd complex
and catalytic reaction with palladacycle 5
5
0.6
Ep= 1.21 V
b
0.4
0.2
a
0.0
ꢀ0.2
ꢀ0.4
0.8
1.0
1.2
1.4
1.6
1.8
ꢀ)
Potential/(V vs Ag/AgCl/Cl
Scheme 3. Cyclic voltammograms recorded on a glassy carbon
electrode (area = 0.03 cm2) at 20 mVs-1 in: (a) AcOH containing
0.1 M of n-Bu4NOAc; (b) solution (a) with 10 mM of
palladacycle 5.
aReaction conditions: 1 (0.25 mmol), Pd(OAc)2 (10 mol%), 2-
phenylacetic acid (1 mmol, 4 eqiuv.), n-Bu4NOAc (0.25 mmol, 1
equiv.), AcOH (3 mL) [anode], n-Bu4NOAc (0.25 mmol, 1 equiv),
AcOH (3 mL) [cathode] in an H-type divide cell with two
platinum electrodes and a Nafion 117 membrane, 60 °C, 8 h.
Isolated yield.
To gain more insight into the process of cross-coupling
reactions, palladacycle
5 was prepared, and the structure was
unambiguously confirmed by X-ray analysis (Scheme 2).15
Catalytic reactions also suggested that this palladacyle is viable
intermediate for C–H cross-coupling reactions (Scheme 2).
Furthermore, a cyclic voltammogram of palladacyle 5, in HOAc
reveals one oxidation wave, at 1.21 V Vs Ag/AgCl (Scheme 3).
This suggests that the anode could oxidize the aryl
palladium(II) intermediate to a high-valent Pd(III) or Pd(IV)
species.16
Scheme 4. Kinetic isotope effect studies
Based on the above experimental results, a plausible
mechanism is proposed for the Pd(II)-catalyzed C(sp2)–H
methylation via electrochemical oxidation (Scheme 5). Initially,
the palladium catalyst coordinates with a nitrogen atom in the
substrate 1a, which brings it in close proximity to the ortho-C–
H
bond. Next, C(sp2)–H activation takes place to give
palladacycle
generated
5. Then
5
could either react with methyl radical18
from MeBF3K or undergo
in-situ
a
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transmetallation19 with MeBF3K under anodic oxidation to
Simke, P. S. Thuy-Boun, D. D. Dixon, J.-Q. Yu, P. S. Baran,
Angew. Chem., Int. Ed. 2013, 52, 7317.
form a Pd(III) or Pd(IV) intermediate
6. Finally, high-valent
6.
For other examples of transition-metal-catalyzed C–H
coupling reactions with alkyl borates, see: a) J. Wippich, I.
Schnapperelle, T. Bach, Chem. Commun. 2015, 51, 3166; b) H.
Wang, S. Yu, Z. Qi, X. Li, Org. Lett. 2015, 17, 2812; c) S. R.
Neufeldt, C. K. Seigerman, M. S. Sanford, Org. Lett. 2013, 15,
2302.
palladium intermediate would undergo a reductive elimination
to release the methylated product 2a and regenerate Pd(II)
species. However, at this stage, we could not rule out the
possibility that this alkylation undergo Pd(II)/Pd(0) catalysis
(Scheme 1c, Path B
).5
7. K. M. Engle, T.-S. Mei, X. Wang, J.-Q. Yu, Angew. Chem., Int. Ed.
2011, 50, 1478.
8.
For selected reviews on electroorganic synthesis, see: a) E. J.
Horn, B. R. Rosen, P. S. Baran, ACS Cent. Sci. 2016, 2, 302; b) P.
Xiong, H.-H. Xu, H.-C. Xu, J. Am. Chem. Soc. 2017, 139, 2956; c)
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12578.
9.
For selected recent examples on anodic C–C cross coupling,
see: a) L. Schulz, M. Enders, B. Elsler, D. Shollmeyer, K. M.
Dyballa, R. Franke, S. R. Waldvogel, Angew. Chem., Int. Ed.
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Chem. Soc. 2016, 138, 8400; c) Z.-W. Hou, Z.-Y. Mao, H.-B.
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electrochemistry, see: a) A. Jutand, Chem. Rev. 2008, 108,
2300; b) W. E. Geiger, Organometallics 2007, 26, 5738.
11. a) K.-J. Jiao, C.-Q. Zhao, P. Fang, T.-S. Mei, Tetrahedron Lett.
2017, 58, 797; b) F. Saito, H. Aiso, T. Kochi, F. Kakiuchi,
Organometallics 2014, 33, 6704; c) F. Kakiuchi; T. Kochi, H.
Mutsutani, N. Kobayashi, S. Urano, M. Sato, S. Nishiyama, T.
Tanabe, J. Am. Chem. Soc. 2009, 131, 11310; d) T. V.
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Scheme 5. Proposed catalytic cycle
In summary, we have demonstrated the first example of
Pd(II)-catalyzed C(sp2)–H methylation and acylation via anodic
oxidation. This process offers an alternative to conventional
methods that require harsh chemical oxidants, and represents
an environmentally conscious method for cross-coupling of
potassium trifluoroalkylborates and α
-keto acids with C(sp2)–H
bonds. Investigations aimed at understanding the reaction
mechanism and further increasing the scope of these reactions
are currently underway in our laboratory.
12. a) Q.-L. Yang, Y.-Q. Li, C. Ma, P. Fang, X.-J. Zhang, T.-S. Mei, J.
Am. Chem. Soc. 2017, 139, 3293; b) Y.-Q. Li, Q.-L. Yang, P.
Fang, T.-S. Mei, D. Zhang, Org. Lett. 2017, 19, 2905.
13. a) J. Luo, N. P. Path, L. M. Mirica, Organometallics 2013, 32,
3343; b) J. R. Khusnutdinova, N. P. Rath, L. M. Mirica, J. Am.
Chem. Soc. 2010, 132, 7303.
Conflicts of interest
14. a) J. Yao, R. Feng, Z. Wu, Z. Liu, Y. Zhang, Adv. Synth. Catal.
2013, 355, 1517; b) J. Miao, H. Ge, Org. Lett. 2013, 15, 2930; c)
P. Fang, M. Li, H. Ge, J. Am. Chem. Soc. 2010, 132, 11898.
There are no conflicts to declare.
Notes and references
15. CCDC
1550234
(5)
contains
the
supplementary
crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic
Data Centre.
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4 | J. Name., 2012, 00, 1-3
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Table of Contents
Palladium-Catalyzed C−H Activation/C–C Cross-Coupling Reactions
via Electrochemistry
Cong Ma, Chuan-Qi Zhao, Yi-Qian Li, Li-Pu Zhang, Xue-Tao Xu, Kun Zhang and Tian-Sheng Mei
Palladium-catalyzed C(sp2)–H methylation and acylation via anodic oxidation have been developed to
avoid the use of stoichiometric chemical oxidants.